CASC3_RAT
ID CASC3_RAT Reviewed; 699 AA.
AC Q8K3X0;
DT 13-APR-2004, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-2002, sequence version 1.
DT 25-MAY-2022, entry version 114.
DE RecName: Full=Protein CASC3;
DE AltName: Full=Cancer susceptibility candidate gene 3 protein homolog;
DE AltName: Full=Metastatic lymph node gene 51 protein homolog {ECO:0000250|UniProtKB:O15234};
DE AltName: Full=Protein barentsz {ECO:0000303|PubMed:12843282};
DE Short=Btz {ECO:0000303|PubMed:12843282};
GN Name=Casc3; Synonyms=Mln51 {ECO:0000250|UniProtKB:O15234};
OS Rattus norvegicus (Rat).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Rattus.
OX NCBI_TaxID=10116;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, HOMOOLIGOMERIZATION, INTERACTION WITH
RP STAU, PHOSPHORYLATION, SUBCELLULAR LOCATION, AND TISSUE SPECIFICITY.
RC STRAIN=Sprague-Dawley;
RX PubMed=12843282; DOI=10.1523/jneurosci.23-13-05778.2003;
RA Macchi P., Kroening S., Palacios I.M., Baldassa S., Grunewald B.,
RA Ambrosino C., Goetze B., Lupas A., St Johnston D., Kiebler M.;
RT "Barentsz, a new component of the Staufen-containing ribonucleoprotein
RT particles in mammalian cells, interacts with Staufen in an RNA-dependent
RT manner.";
RL J. Neurosci. 23:5778-5788(2003).
RN [2]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-145; SER-262; SER-360 AND
RP SER-370, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22673903; DOI=10.1038/ncomms1871;
RA Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA Olsen J.V.;
RT "Quantitative maps of protein phosphorylation sites across 14 different rat
RT organs and tissues.";
RL Nat. Commun. 3:876-876(2012).
CC -!- FUNCTION: Required for pre-mRNA splicing as component of the
CC spliceosome (By similarity). Core component of the splicing-dependent
CC multiprotein exon junction complex (EJC) deposited at splice junctions
CC on mRNAs. The EJC is a dynamic structure consisting of core proteins
CC and several peripheral nuclear and cytoplasmic associated factors that
CC join the complex only transiently either during EJC assembly or during
CC subsequent mRNA metabolism. The EJC marks the position of the exon-exon
CC junction in the mature mRNA for the gene expression machinery and the
CC core components remain bound to spliced mRNAs throughout all stages of
CC mRNA metabolism thereby influencing downstream processes including
CC nuclear mRNA export, subcellular mRNA localization, translation
CC efficiency and nonsense-mediated mRNA decay (NMD). Stimulates the
CC ATPase and RNA-helicase activities of EIF4A3. Plays a role in the
CC stress response by participating in cytoplasmic stress granules
CC assembly and by favoring cell recovery following stress. Component of
CC the dendritic ribonucleoprotein particles (RNPs) in hippocampal
CC neurons. May play a role in mRNA transport. Binds spliced mRNA in
CC sequence-independent manner, 20-24 nucleotides upstream of mRNA exon-
CC exon junctions. Binds poly(G) and poly(U) RNA homomer (By similarity).
CC Component of the dendritic ribonucleoprotein particles (RNPs) in
CC hippocampal neurons. May play a role in mRNA transport.
CC {ECO:0000250|UniProtKB:O15234, ECO:0000269|PubMed:12843282}.
CC -!- SUBUNIT: Identified in the spliceosome C complex (By similarity).
CC Component of the mRNA splicing-dependent exon junction complex (EJC),
CC which contains at least CASC3, EIF4A3, MAGOH, NXF1 and RBM8A/Y14.
CC Identified in a complex composed of the EJC core, UPF3B and UPF2. The
CC EJC core can also interact with UPF3A (in vitro) (By similarity). Forms
CC homooligomers (PubMed:12843282). Interacts with STAU in an RNA-
CC dependent manner (PubMed:12843282). Interacts with DHX34; the
CC interaction is RNA-independent (By similarity).
CC {ECO:0000250|UniProtKB:O15234, ECO:0000269|PubMed:12843282}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000269|PubMed:12843282}.
CC Cytoplasm, perinuclear region {ECO:0000269|PubMed:12843282}. Nucleus
CC {ECO:0000250|UniProtKB:Q8K3W3}. Nucleus speckle
CC {ECO:0000250|UniProtKB:O15234}. Cytoplasm, Stress granule
CC {ECO:0000250|UniProtKB:O15234}. Cell projection, dendrite
CC {ECO:0000269|PubMed:12843282}. Note=Shuttles between the nucleus and
CC the cytoplasm in a XPO1/CRM1-dependent manner (By similarity).
CC Transported to the cytoplasm as part of the exon junction complex (EJC)
CC bound to mRNA. In nuclear speckles, colocalizes with MAGOH. Under
CC stress conditions, colocalizes with FMR1 and TIA1, but not MAGOH and
CC RBM8A EJC core factors, in cytoplasmic stress granules (By similarity).
CC In the dendrites of hippocampal neurons, localizes to dendritic
CC ribonucleoprotein granules (Probable). {ECO:0000250|UniProtKB:O15234,
CC ECO:0000250|UniProtKB:Q8K3W3, ECO:0000305|PubMed:12843282}.
CC -!- TISSUE SPECIFICITY: Expressed in the brain, including in the
CC hippocampus (at protein level). {ECO:0000269|PubMed:12843282}.
CC -!- DOMAIN: The coiled coil domain may be involved in oligomerization.
CC -!- PTM: Phosphorylated. {ECO:0000269|PubMed:12843282}.
CC -!- PTM: ADP-ribosylated by tankyrase TNKS and TNKS2. Poly-ADP-ribosylated
CC protein is recognized by RNF146, followed by ubiquitination (By
CC similarity). {ECO:0000250}.
CC -!- PTM: Ubiquitinated by RNF146 when poly-ADP-ribosylated, leading to its
CC degradation. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the CASC3 family. {ECO:0000305}.
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DR EMBL; AF525467; AAM88386.1; -; mRNA.
DR RefSeq; NP_671485.1; NM_147144.1.
DR AlphaFoldDB; Q8K3X0; -.
DR BioGRID; 251708; 1.
DR STRING; 10116.ENSRNOP00000013204; -.
DR iPTMnet; Q8K3X0; -.
DR PhosphoSitePlus; Q8K3X0; -.
DR jPOST; Q8K3X0; -.
DR PaxDb; Q8K3X0; -.
DR PRIDE; Q8K3X0; -.
DR GeneID; 259170; -.
DR KEGG; rno:259170; -.
DR UCSC; RGD:628766; rat.
DR CTD; 22794; -.
DR RGD; 628766; Casc3.
DR eggNOG; KOG4264; Eukaryota.
DR InParanoid; Q8K3X0; -.
DR OrthoDB; 486761at2759; -.
DR PhylomeDB; Q8K3X0; -.
DR Reactome; R-RNO-159236; Transport of Mature mRNA derived from an Intron-Containing Transcript.
DR Reactome; R-RNO-72187; mRNA 3'-end processing.
DR Reactome; R-RNO-73856; RNA Polymerase II Transcription Termination.
DR Reactome; R-RNO-975957; Nonsense Mediated Decay (NMD) enhanced by the Exon Junction Complex (EJC).
DR PRO; PR:Q8K3X0; -.
DR Proteomes; UP000002494; Unplaced.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0010494; C:cytoplasmic stress granule; IEA:UniProtKB-SubCell.
DR GO; GO:0030425; C:dendrite; IEA:UniProtKB-SubCell.
DR GO; GO:0035145; C:exon-exon junction complex; ISO:RGD.
DR GO; GO:0016607; C:nuclear speck; IEA:UniProtKB-SubCell.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:1990904; C:ribonucleoprotein complex; ISO:RGD.
DR GO; GO:0071006; C:U2-type catalytic step 1 spliceosome; ISS:UniProtKB.
DR GO; GO:0019899; F:enzyme binding; ISO:RGD.
DR GO; GO:0042802; F:identical protein binding; ISO:RGD.
DR GO; GO:0003729; F:mRNA binding; IEA:InterPro.
DR GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:RGD.
DR GO; GO:0008298; P:intracellular mRNA localization; ISO:RGD.
DR GO; GO:0000398; P:mRNA splicing, via spliceosome; ISS:UniProtKB.
DR GO; GO:0051028; P:mRNA transport; IEA:UniProtKB-KW.
DR GO; GO:0000184; P:nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; IEA:UniProtKB-KW.
DR GO; GO:2000622; P:regulation of nuclear-transcribed mRNA catabolic process, nonsense-mediated decay; ISO:RGD.
DR GO; GO:0006417; P:regulation of translation; IEA:UniProtKB-KW.
DR InterPro; IPR018545; Btz_dom.
DR InterPro; IPR028544; CASC3.
DR PANTHER; PTHR13434; PTHR13434; 1.
DR Pfam; PF09405; Btz; 1.
DR SMART; SM01044; Btz; 1.
PE 1: Evidence at protein level;
KW ADP-ribosylation; Cell projection; Coiled coil; Cytoplasm; mRNA processing;
KW mRNA splicing; mRNA transport; Nonsense-mediated mRNA decay; Nucleus;
KW Phosphoprotein; Reference proteome; RNA-binding; Spliceosome;
KW Stress response; Translation regulation; Transport; Ubl conjugation.
FT CHAIN 1..699
FT /note="Protein CASC3"
FT /id="PRO_0000089326"
FT REGION 1..455
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 134..280
FT /note="Necessary for RNA-binding, interaction with MAGOH
FT and localization in nucleus speckles"
FT /evidence="ECO:0000250"
FT REGION 134..280
FT /note="Sufficient to form the EJC"
FT /evidence="ECO:0000250"
FT REGION 374..699
FT /note="Necessary for localization in cytoplasmic stress
FT granules"
FT /evidence="ECO:0000250"
FT REGION 577..596
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 629..699
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COILED 93..128
FT /evidence="ECO:0000255"
FT MOTIF 201..207
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000255"
FT MOTIF 251..259
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000255"
FT MOTIF 458..467
FT /note="Nuclear export signal"
FT COMPBIAS 1..15
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 76..106
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 107..138
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 154..229
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 298..316
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 336..357
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 392..415
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 582..596
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 633..649
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 650..669
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 670..688
FT /note="Pro residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 34
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:Q8K3W3"
FT MOD_RES 115
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15234"
FT MOD_RES 145
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 262
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 354
FT /note="Phosphothreonine"
FT /evidence="ECO:0000250|UniProtKB:O15234"
FT MOD_RES 360
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 370
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:22673903"
FT MOD_RES 473
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:O15234"
SQ SEQUENCE 699 AA; 75904 MW; C5D33730761A6224 CRC64;
MADRRRQRAS QDTEDEESGA SGSDSGSPAR GGGSCSGSAG GGGSGSLPSQ RGGRGGGLHL
RRVESGGAKS AEESECESED GMEGDAVLSD YESAEDSEGE EEYSEEENSK VELKSEANDA
ADSSAKEKGE EKPESKGTVT GERQSGDGQE STEPVENKVG KKGPKHLDDD EDRKNPAYIP
RKGLFFEHDL RGQTQEEEVR PKGRQRKLWK DEGRWEHDKF REDEQAPKSR QELIALYGYD
IRSAHNPDDI KPRRIRKPRF GSPPQRDPNW IGDRSSKSHR HQGPGGNLPP RTFINRNAAG
TGRMSTSRNY SRSGGFKEGR TSFRPVEVGG QHGARSGETL KHEANYRSRR LEQTPMRDPS
PEPDAPLLGS PEKEEVASET PAAVPDITPP APDRPIEKKS YSRARRTRTK VGDAVKAAEE
VPPPSEGLTS AATVPESTPP AAKTGNWEAP VDSTTGGLEQ DVAQLNIAEQ NWSPGQPSFL
QPRELRGMPN HIHMGAGPPP QFNRMEEMGV QSGRAKRYSS QRQRPVPEPP APPVHISIME
GHYYDPLQFQ GPIYTHGDSP APLPPQGMIV QPEMHLPHPG LHPHQSPAPL PNPGLYPPPV
SMSPGQPPPQ QLLAPTYFSA PGVMNFGNPS YPYAPGALPP PPPPHLYPNT QAPSQVYGGV
TYYNPAQQQV QPKPSPPRRT PQPVSIKPPP SEVVSRGSS
